Abstract
In addition to aging, lifestyle, and environmental conditions, numerous structural and functional changes can alter the cardiovascular function. Health management is aimed at preventing or, at least, attenuating evolution rate by targeting risk factors, that is, supporting healthy eating and exercise and avoiding smoking tobacco, as well as screening populations at risk.
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Notes
- 1.
Sources: Cité de la Science in Paris and European Health Status publication of the European Commission.
- 2.
Flavonoids (Latin flavus: yellow [golden or reddish yellow]) constitute a set of plant ketone-containing metabolites that comprise: (1) flavones derived from 2-phenylchromen 2-phenyl (1,4)-benzopyrone; (2) isoflavonoids derived from 3-phenylchromen 3-phenyl (1,4)-benzopyrone; and (3) neoflavonoids derived from 4-phenylcoumarine 4-phenyl (1,2)-benzopyrone. Flavanoids, a.k.a. flavan-3-ols and catechins, are nonketone polyhydroxy polyphenol compounds that share with flavonoids a 2-phenyl (3,4)-dihydro 2H-chromen 3-ol skeleton. Flavonoids (flavonols and flavanols) may have antiallergic, anti-inflammatory, antioxidant, antimicrobial, and anticancer effects.
- 3.
These channels are composed of the pore-forming Slo1 and an auxiliary subunit. DHA activates vascular Slo1–\({}_{\mathrm{BK}}{\upbeta}\)1 and neuronal Slo1–\({}_{\mathrm{BK}}{\upbeta}\)4 channels [114]. Stimulation by DHA has a much smaller effect on Slo1–\({}_{\mathrm{BK}}{\upbeta}\)2 and Slo1–\({}_{\mathrm{BK}}{\upgamma}\)1 channels [114].
- 4.
Allicin, the main organosulfur compound, is produced from amino acid alliin by alliinase and rapidly decomposes mainly into diallyl sulfide, disulfide, and trisulfide, and ajoene. After consumption, these compounds are rapidly metabolized.
- 5.
The free radical nitric oxide can be added to unsaturated and hydroperoxy fatty acids. Nitrated fatty acids result from the reaction of nitrogen dioxide with unsaturated fatty acids. The NO\(_2^{\bullet}\) radical can form, according to the local oxygen concentration, nitronitrite and nitroallyl derivatives as well as lipid hydroperoxide. Nitrated derivatives of unsaturated fatty acids are formed under oxidative and nitrative stresses. In biological tissues, nitrofatty acids are produced by nonenzymatic reactions not only with NO\(^{\bullet}\) and NO\(_2^{\bullet}\), but also with peroxynitrite (ONOO\(^-\)). Nitrofatty acids lodge in membrane phospholipids. Nitrated derivatives of arachidonic, eicosapentaenoic, linoleic, linolenic, oleic, and palmitoleic acids and their nitrohydroxy derivatives (nitrohydroxy oleate, linoleate and linolenate) can be also detected in human plasma and urine. In plasma, nitrofatty acids are free, bound reversibly to thiol-containing proteins, and esterified (as cholesterol esters). In plasma, nitrofatty acids are stabilized by incorporation into lipoproteins. Nitrofatty acids modulate macrophage activation, prevent leukocyte and platelet activation, and promote vascular relaxation [122].
- 6.
In unstressed conditions, NFE2L2 is permanently ubiquitinated by the Cul3–(KEAP1)\(_2\) protein–ubiquitin ligase complex and rapidly degraded in proteasomes. The KEAP1 homodimer binds to a single NFE2L2 molecule. Upon exposure to electrophilic and oxidative stresses, KEAP1 is modified and its ubiquitin ligase activity declines, thereby stabilizing NFE2L2 to induce cytoprotective gene transcription.
- 7.
Humans regularly exposed to sunlight synthesize adequate concentrations of vitamin-D. Solar ultraviolet-B waves convert 7-dehydrocholesterol to previtamin-D\(_3\) (or precholecalciferol), which spontaneously isomerizes to vitamin-D\(_3\) (cholecalciferol). Otherwise, few food components contain sufficient vitamin-D, such as fish liver, fatty fish, and egg yolks. Vitamin-D receptor lodges in myocardial and vascular cells. Calcitriol represses the renin–aldosterone axis, causes insulin secretion and sensitivity, prevents proliferation of vascular smooth myocytes and hypertrophy of cardiomyocytes, and can exert immunoregulatory functions.
- 8.
NPY: neuropeptide-Y; AgRP: agouti-related protein homolog.
- 9.
POMC: proopiomelanocortin.
- 10.
Ghrelin and motilin are coproduced in the same cells in the duodenum and jejunum and stored in all secretory granules in these cells before being cosecreted [129]. In addition, preproghrelin not only gives rise to orexigenic ghrelin, but also obestatin, a ghrelin antagonist [130].
- 11.
Ghrelin is a potent GHS, once it is processed by ghrelin \({}^{\mathrm{O}}\)acyl transferase.
- 12.
Four types of endocrine cells, D, enterochromaffin (EC), enterochromaffin-like (ECL), and P/D1 cells, have been identified in the oxyntic mucosa. Major products stored in granules of D, EC, ECL, and P/D1 cells are somatostatin, serotonin, histamine and uroguanylin, and ghrelin, respectively,
- 13.
TLR4 polymorphism is not associated with the risk of developing asthma, but genetically determined hyporesponsiveness to lipopolysaccharide can increase atopy severity [133].
- 14.
Among nicotinic acetylcholine receptors, which are pentameric ligand-gated ion channels, in vascular smooth myocytes, the homomeric \({\upalpha}\)7-nAChR possesses high Ca\(^{2+}\) permeability and rapid onset of desensitization.
- 15.
The pressure–flow relation is an Ohm-like law. In electricity, the Ohm law states that the current (i) through a conductor between two points is proportional to the potential difference (u) between these two points. The constant of proportionality is the resistance (\(u~=~{\tt R}\,i\)).
- 16.
Protein RhoGEF12 is activated by the interaction of G\({\upalpha}_{12}\) with G\({\upalpha}_{13}\) subunit.
- 17.
\({\updelta}{\upiota}{\upalpha}{\upbeta}{\upeta}{\uptau}{\upeta}{\upsigma}\): compass (Latin: diabetes).
- 18.
A.k.a. cationic amino acid transporter CAT1 and system y\(^+\) basic amino acid transporter.
- 19.
A.k.a. equilibrative (nitrobenzylmercaptopurine riboside [NBMPR]-sensitive) nucleoside transporter ENT1.
- 20.
A.k.a. growth arrest and DNA-damage-inducible protein GADD153.
- 21.
Nitric oxide modulates expression and activity of transcription factors, such as CHOP–C/EBP\({\upalpha}\), NF\({\upkappa}\)B, GATA, Activator protein-1, and interferon regulatory factor IRF1 in endotheliocytes [147]. Nitric oxide represses Vcam1 gene transcription via NF\({\upkappa}\)B in human aortic and saphenous vein smooth myocytes.
- 22.
Two cardiac adipose tissue depots include [148]: (1) epicardial adipose tissue between the myocardium and visceral pericardium, which localizes to both ventricles in the atrioventricular and interventricular grooves extending to the apex and along the coronary arteries, and (2) pericardial adipose tissue outside the inner layer of the pericardium, which covers 80 % of the heart surface. The volume of epicardial fat increases in patients with coronary artery disease and unstable angina with respect to healthy individuals.
- 23.
The 36-amino acid peptide Tyr–Tyr (PYY) is secreted by the neuroendocrine cells of the mucosa of the gastrointestinal tract, especially the ileum and colon, in response to a meal.
- 24.
The onset of the R-wave yields the initial time at the aortic valve. The peripheral measurement station is usually the fingertip, where the pressure wave is detected by a photoplethysmographic probe. The virtual base point of the photoplethysmographic signal corresponds to the intersection point between the tangent to the pulse wave at the point with the maximal slope during the systolic rise and the horizontal line crossing the minimal pressure point.
- 25.
Hypopneas are defined as a clear and discernible reduction in flow (> 50 %) that ended with an arousal and fall in \(S_{\mathrm{a}_{\mathrm{O}_2}}\) of at least 3 %. UAREs refer to as flow limitation without flow reduction occurring concurrently with an increasing esophageal pressure (or surrogate PTT), ending with an arousal, and followed by a return of the esophageal pressure to its resting level.
- 26.
Air pollution is lower on rainy rather than on sunny days.
- 27.
\({\upmu}{\upupsilon}{\upkappa}{\upeta}\varsigma\): fungus, \({\uptau}\)o\({\upxi}{\upiota}{\upkappa}\)o\({\upnu}\): poison on an arrow (\({\uptau}\)o\({\upxi}{\epsilon}{\upupsilon}{\upmu}{\upalpha}\)). A given fungus can produce many types of mycotoxins. A given mycotoxin can be produced by several species of fungi. These toxic secondary metabolites colonize crops.
- 28.
Cytochrome-P450 enzymes convert aflatoxins to the reactive (8,9)-epoxide form that can bind to DNA and proteins, hence their carcinogenicity.
- 29.
Fumonisins interfere with sphingolipid metabolism in animals.
- 30.
Several ergot alkaloids induce smooth muscle contractions. Ergotism comprises gangrenous and convulsive forms. In animals, ergotism causes gangrene, abortion, suppression of lactation, hypersensitivity, convulsions, and ataxia [172].
- 31.
SNPs constitute a large fraction of variations of the human genome. Two alleles of each SNP have different frequencies in the population. Additional variations comprise insertions, deletions, and structural variations, as well as epigenetic modifications.
- 32.
Arterial tortuosity syndrome is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis, and aneurysm in major arteries that results from disruption of medial elastic fibers in the arterial wall.
- 33.
Strong correlations are found with the catalytic subunit of the myosin light chain phosphatase, A-kinase anchoring protein AKAP9, regulatory subunit \({}^{{\mathrm{P}}85\alpha}\)PI3K\(_{{\mathrm{r}}1}\) of phosphoinositide 3-kinase, protein kinase-C\({\upbeta}\)1, and synaptojanin-1.
- 34.
Concentrations of integrin-\({\upalpha}_{2\mathrm{B}}\), \({\upalpha}_6\), \({\upbeta}_3\), and \({\upbeta}_5\) differ between stiff and distensible aortas. Certain proteoglycans, decorin, osteomodulin, aggrecan-1, and chondroitin sulfate proteoglycan-5 (neuroglycan-C), and related proteins, dermatopontin (a decorin-binding proteoglycan), have different amounts between stiff and distensible aortas.
- 35.
The Ala457Pro exchange, or A457P variation, is defined by a Pro457 mutant and Ala457 wild-type forms.
- 36.
The A369P polymorphism (relatively high allele frequency) leads to intracellularly retention and hence lack of noradrenaline transport. Like A457P polymorphism, A369P and N292T polymorphisms exert a dominant negative effect on wild-type SLC6a2 transporter [179]. Other gene variants (T182C and A3081T) alter SLC6A2 promoter activity; they are associated with pressor response during exercise, but not with cardiac frequency and plasma catecholamine changes.
- 37.
The ANGPTL3 gene encodes angiopoietin-like protein-3 that influences triglyceride metabolism.
- 38.
The MLXIPL gene encodes carbohydrate-response element-binding protein. This transcription factor connects hepatic carbohydrate flux to fatty-acid synthesis.
- 39.
The GALNT2 gene encodes \({}^{\mathrm{N}}\)acetylgalactosaminyltransferase-2 involved in O-linked glycosylation.
- 40.
The chromosome 1 is the largest human chromosome, with more than 249 × 10\(^6\) nucleotide base pairs [182].
- 41.
This acronym also refers to as coronary heart disease. It is thus avoided.
- 42.
Transcription factors Tbx5 and Nkx2-5 interact and synergistically activate their downstream targets. Defective interactions between GATA4 and NKX2-5 and between GATA4 and TBX5 might underlie congenital heart diseases caused by GATA4 mutations.
- 43.
The shorter chromosome arm is called p arm (from French petit: small) and longer arm q arm (in alphabetical order for increasing size).
- 44.
The ventricle relaxation has 2 components: (1) an active component during which cardiomyocytes relax after each contraction with regulated Ca\(^{2+}\) removal from the cytosol, and (2) a subsequent passive component during which the ventricle distends due to blood influx from the atria.
- 45.
The TFAP2B gene encodes transcription factor activating enhancer-binding protein-2\({\upbeta}\).
- 46.
The MED13L gene encodes Mediator complex subunit-13-like protein, or thyroid hormone receptor-associated protein THRAP2.
- 47.
Among 6 long noncoding RNAs (lncRNA) and large intergenic noncoding RNAs (lincRNA) according to whether they are encoded intra- or intergenically, respectively, that possess hypoxia response elements (HRE) in their gene promoters, only lincRNAp21 is boosted by hypoxia [195]. It enables hypoxia-induced changes in metabolism, favoring hypoxia-enhanced glycolysis. Moreover, it protects HIF1\({\upalpha}\) against its degradation, as it interacts with both HIF1\({\upalpha}\) and VHL ubiquitin ligase and competitively disrupts the VHL–HIF1\({\upalpha}\) interaction, thereby assisting HIF1\({\upalpha}\) stability in response to hypoxia. Conversely, HIF1\({\upalpha}\) supports the hypoxia-induced increase in lincRNAp21 level, which is a HIF1\({\upalpha}\) transcriptional target (positive feedback).
- 48.
A.k.a. TRAF6-regulated IKK activator-1\({\upbeta}\).
- 49.
Oncogenes reduce the Ca\(^{2+}\) level in the endoplasmic reticulum. Cancer-related microRNAs lower the expression of the mitochondrial Ca\(^{2+}\) uniporter, thus reducing sensitivity to apoptosis. On the other hand, tumor suppressors have the opposite effect [198].
- 50.
Troponin-I is phosphorylated (Ser23/Ser24) by PKA upon \({\upbeta}\)-adrenergic receptor stimulation, enabling positive lusitropy. Protein kinase-G, various PKC isoforms, and PKC-activated enzymes, such as \({}^{\mathrm{P}90}\)RSK and PKD also target this phosphorylation site. Protein kinase-C phosphorylates other sites (Ser43/Ser45 and Thr144).
- 51.
Troponin-T phosphorylation (Thr206) by PKC or cRaf decreases maximum force and myofilament Ca\(^{2+}\) sensitivity. Both PKC and MAP3K5 phosphorylate cTnnT at other sites. Protein kinase-A and -G phosphorylate cTnnI only when anchored to cTnnT.
- 52.
In humans, AKIP1 has 3 splice variants, full-length protein (AKIP1a), a subtype encoded by a transcript lacking exon 3 (AKIP1b), and another by a transcript lacking exon-3 and -5 (AKIP1c). Isoform AKIP1b recruits the histone deacetylase sirtuin-1 upon neddylation that represses gene transcription. On the other hand, AKIP1a recruits NF\({\upkappa}\) B in a PKA-dependent manner and enhances gene transcription. In the nucleus, AKIP1 enhances the PKA–NF\({\upkappa}\) B–SIRT1 axis. Another role takes place at mitochondria.
- 53.
In mitochondria, the apoptosis-inducing factor may stabilize \({}^{\mathrm{ETC}}\)complex-I. This death effector is released from mitochondria and translocates to the nucleus. In the nucleus, it causes chromatin condensation and DNA fragmentation. Protein AKIP1 interacts with AIF and sequesters AIF to mitochondria, thereby preventing cell death.
- 54.
Glutamate released from the presynaptic neuron activates GluN\(_1\) (\({}^{\mathrm{NMDA}}\)Glu) receptor and provokes a calcium influx that stimulates NOS2 linked to DLg4 anchoring protein attached to GluN\(_1\) via calmodulin. Nitric oxide produced in the postsynaptic neuron can then diffuse to the presynaptic neuron or neighboring cells (neurons or astrocytes) to activate sGC that synthesizes cGMP (in both pre- and postsynaptic neurons) [142]. Messenger cGMP can then influence activity of ion channels, phosphodiesterases, and protein kinases.
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Thiriet, M. (2015). Context of Cardiac Diseases. In: Diseases of the Cardiac Pump. Biomathematical and Biomechanical Modeling of the Circulatory and Ventilatory Systems, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-12664-7_2
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